Identification of potential miRNA-mRNA interaction network in bone marrow T cells of acquired aplastic anemia

Hematology. 2020 Dec;25(1):168-175. doi: 10.1080/16078454.2020.1757332.

Abstract

Background: MicroRNAs(miRNAs) can regulate T cell differentiation and plasticity by targeting their corresponding message RNAs (mRNAs), which play important roles in many autoimmune diseases. But the effect of miRNAs and their targeted mRNAs in acquired AA is not fully understood.Methods: The Gene Expression Omnibus data-sets of bone marrow T cells in acquired AA patients were performed to integrated analysis. Differently expressed miRNAs (DE-miRNAs) and mRNAs (DE-mRNAs) were identified. Target mRNAs of DE-miRNAs predicted by miRNet were compared with DE-mRNAs, the intersection mRNAs of two groups were negatively matched with the DE-miRNAs and defined as dysregulated mRNAs. GO and KEGG analyses for dysregulated mRNAs were performed. Protein-protein interaction (PPI) networks for dysregulated mRNAs were established. Modules in the PPI networks were identified, and the miRNA-mRNA networks were constructed.Results: 40 DE-miRNAs and 1511 DE-mRNAs were accessed. 303 negative correlation pairs of miRNA-mRNA were identified. Hsa-mir-34a-5p, hsa-mir-195-5p and hsa-mir-424-5p may be the central hubs. GO and KEGG analyses revealed that dysregulated mRNAs were involved in T cell differentiation and plasticity. Finally, the miRNA-mRNA networks were constructed. Has-mir-34a-5p, hsa-mir-195-5p and hsa-mir-424-5p were all involved in the central network and the target mRNA for them were histone genes and histone methylation gene KMT2D.Conclusion: The miRNA-mRNA network in our study show that hsa-mir-34a-5p, hsa-mir-195-5p, and hsa-mir-424-5p may regulate the T cell differentiation and plasticity by targeting histone gene expression and histone modification.

Keywords: MicroRNAs (miRNAs); T cells; aplastic anemia (AA); bioinformatic analysis; bone marrow; histone expression; histone modification; message RNAs (mRNAs).

MeSH terms

  • Anemia, Aplastic / genetics*
  • Bone Marrow / metabolism*
  • Gene Regulatory Networks / genetics*
  • Humans
  • MicroRNAs / genetics*
  • T-Lymphocytes / metabolism*

Substances

  • MicroRNAs